e18043 Background: Neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS), is a possible approach to patients with stages IIIC and IV epithelial ovarian cancer who are most likely to have suboptimal results with upfront surgery. Delay in initiation of adjuvant chemotherapy has been associated with worse outcomes. Our study aimed to evaluate whether time from NACT to surgery (TNS) and from surgery to adjuvant chemotherapy (TSA) were associated with survival outcomes and with platinum-resistant relapse. Methods: We did a retrospective analysis of medical records from 194 patients with EOC treated with IDS at a single institution from 2007 to 2018. We calculated the median TNS and TSA and evaluated its relation to progression free survival (PFS), overall survival (OS) and time to platinum-resistant relapse (TTPR) through Kaplan-Meier and Cox regression analysis. Results: After a median follow-up of 62 months, OS was 58 months and PFS was 18 months. Most patients received at least 3 cycles of NACT (21.1% 3 cycles, 16.0% 4 cycles and 39.7% 6 cycles); and the rate of optimal cytoreduction was 75,8%. Optimal surgery was associated with survival (p < 0.001). TNS over 8 weeks and TSA over 7 weeks were associated with worse PFS (HR 1.57, 95%CI 1.07-2.31; HR 1.52, 95%CI 1.00-2.32, respectively) and OS (HR 1.83, 95%CI 1.13-2.96; HR 1.57, 95%CI 0.93-2.65, respectively) in univariate analysis but not in a multivariate analysis including residual disease as a covariate. In the subgroup of patients with residual disease < 10mm a multivariate analysis showed shorter PFS (HR 2.06, CI95% 1.16-3.66, p = 0.014) and OS (HR 2.20, CI95% 1.05-4.59, p = 0.035) for patients with TSA longer than 7 weeks. Longer TNS was associated with PFS (HR 1.66, 95%CI 1.06-2.59, p = 0.026) in univariate analysis but not in multivariate analysis. Interestingly, longer TNS was associated with shorter TTPR (65.6 vs. 35.0 months, p = 0.049) and a higher frequency of platinum resistant relapse at first relapse (48.8% versus 26.5%, p = 0.012). Conclusions: Our study provides evidence that delayed TSA is an independent prognostic factor for worse PFS and OS only in the subgroup of patients with residual disease ≤ 10mm. Longer TNS was associated with higher risk of platinum resistant relapse. One possible explanation is that NACT may select chemoresistant clones, which would have more time to grow and spread with longer intervals until surgery. Further studies are necessary to corroborate this hypothesis.
6076 Background: Germline BRCA pathogenic variants are present in 15% to 25% of ovarian carcinoma patients. These tumors are more sensitive to platinum and PARP inhibitor therapy and have a better prognosis. Two retrospective studies with limited number of patients have shown conflicting results regarding the benefit of secondary cytoreductive surgery (SCS) in patients with BRCA mutations. Our aim was to evaluate the impact of SCS in recurrent ovarian cancer according to BRCA status. Methods: All patients with ovarian carcinoma with recurrent disease and who were tested for BRCA pathogenic variants treated at a tertiary Cancer Center in Brazil were included. Patients characteristics were compared between patients treated with SCS and not treated with SCS. Cox regression analysis was used to evaluate the impact of SCS on progression free survival (PFS) and the influence of BRCA pathogenic variants on the effect of SCS. Results: One hundred and forty patients were included, 49.6% were treated with SCS and chemotherapy and 50.4% treated with chemotherapy only. Patients treated with SCS were younger, presented better performance status, lower CA 125 and longer platinum free interval. After adjusting for relevant covariables SCS was associated with longer PFS (HR 0.53, 95%CI 0.29-0.97, p = 0.039). Germline BRCA pathogenic variants were found in 37 patients (26.4%). No patient was treated with PARP inhibitors. Among non-carriers of pathogenic variants in BRCA, SCS lead to a longer PFS (HR 0.48, 95%CI 0.28-0.81, p = 0.006) but among carriers there was no benefit of SCS (HR 0.84, 95%CI 0.30-2.34, p = 0.735). Test for interaction was not statistically significant (p = 0.359). Conclusions: Our study is the second to demonstrate no benefit of SCS among patients with BRCA pathogenic variants and not treated with PARP inhibitor. The only other study to show a benefit of SCS in this group of patients included a limited number of patients and all of them were treated with PARP inhibitors. BRCA germline status might influence the efficacy of SCS, and should be evaluated as a potential biomarker to be assessed together with clinical factors to better select patients for SCS.
Background Benefit of carboplatin and dose-dense weekly paclitaxel (ddCT) in first line treatment of ovarian cancer patients has been different in Western and Asian studies. In the present study we compare progression-free survival (PFS) of ddCT to three-weekly carboplatin and paclitaxel (CT) in first-line treatment of ovarian carcinoma in a single institution in a Western population. Materials and methods We conducted a retrospective review of medical records from patients with ovarian carcinoma treated in a tertiary cancer center from 2007 to 2018. All patients treated with ddCT or CT in the first-line setting were included. Patients who received first-line bevacizumab were not included. PFS and overall survival (OS) were compared in a propensity score-matched cohort to address selection bias. Patients were matched according to age, ECOG performance status, CA 125, FIGO stage, residual disease, and histological subtype, in a 1:2 ratio. Results Five hundred eighty-eight patients were eligible for propensity score matching, the final cohort consisted of 69 patients treated with ddCT and 138 CT group. Baseline characteristics were well-balanced. After a median follow-up of 65.1 months, median PFS was 29.3 vs 20.0 months, favouring ddCT treatment (p = 0.035). In the multivariate cox regression ddCT showed a 18% lower risk of progression (HR 0.82, 95% CI 0.68–0.99, p = 0.04). Overall survival data is immature, but suggested better outcomes for ddCT (not reached versus 78.8 months; p = 0.07). Conclusion Our retrospective study has shown superior PFS of ddCT over CT regimen in first-line treatment of ovarian carcinoma in a Western population not treated with bevacizumab.
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